A Study of Renal Function in Treatment-naïve, Young Male Patients With Fabry Disease

A Cross-sectional Study of Renal Function in Treatment-naïve, Young Male Patients With Fabry Disease

No investigational drug will be administered in this study for the treatment of Fabry disease.

This will be a multicenter, multinational, non-treatment, cross-sectional study of young male patients with Fabry disease who have not yet initiated interventional treatment for this disease. The study will consist of a screening visit(s), a clinical investigation visit(s), and a follow-up phone contact.

The objectives of the study are:

• To document renal function and other Fabry disease manifestations across age in treatment-naïve, young male patients with Fabry disease.
• To provide a reference group for comparison with interventional clinical trials of Fabry disease.

The duration of each patient's participation in the study, inclusive of the screening visit and follow-up phone contact, will be approximately 12 weeks.

Study Overview

• Status: Terminated
• Conditions: Fabry Disease
• Intervention / Treatment: Drug: Iohexol

Detailed Description

Patients who meet all eligibility criteria based on screening assessments will be scheduled to return to the clinic for assessments of renal function and other disease-related parameters, which may be scheduled over one or more clinical investigation visits. The clinical investigation visit(s) will be scheduled such that renal and cardiac assessments occur after the required medication washout (see exclusion criterion); other procedures may be performed either before or after the medication washout, at the discretion of the investigator.

Up to 100 patients will be enrolled in the study, including a minimum of 15 patients in each of the following age groups (based on age at screening): 5 to 11 years, 12 to 17 years, and 18 to 25 years.

All patients will be encouraged to enroll in the Fabry Registry (NCT00196742) for continued follow-up after completion of the study.

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 1

Contacts and Locations

Study Locations

• Argentina
  • Capital Federal, Argentina, 1425
    • Investigational Site Number 032001
• Austria
  • Wien, Austria, 1090
    • Investigational Site Number 040001
• Belgium
  • Liège, Belgium, 4000
    • Investigational Site Number 056001
• Brazil
  • Porto Alegre, Brazil, 90035 003
    • Investigational Site Number 076001
• Canada
  • Montreal, Canada, H4J 1C5
    • Investigational Site Number 124001
  • Toronto, Canada, M5G 1X8
    • Investigational Site Number 124004
• Finland
  • Vaasa, Finland, 65130
    • Investigational Site Number 246002
• France
  • Bron Cedex, France, 69677
    • Investigational Site Number 250002
  • Garches, France, 92380
    • Investigational Site Number 250001
• Hungary
  • Pécs, Hungary, 7623
    • Investigational Site Number 348001
• Norway
  • Bergen, Norway, 5021
    • Investigational Site Number 578001
• Poland
  • Warszawa, Poland, 04-730
    • Investigational Site Number 616001
• Spain
  • Badalona, Spain, 08916
    • Investigational Site Number 724001
  • Girona, Spain, 17007
    • Investigational Site Number 724002
• Taiwan
  • Taipai, Taiwan, 10043
    • Investigational Site Number 158001
• United Kingdom
  • London, United Kingdom, NW1 2PJ
    • Investigational Site Number 826004
  • London, United Kingdom, WC1N 3JH
    • Investigational Site Number 826002
• United States
  • California
    • La Jolla, California, United States, 92093
      • Investigational Site Number 840010
  • Georgia
    • Decatur, Georgia, United States, 30033
      • Investigational Site Number 840006
  • Ohio
    • Cincinnati, Ohio, United States, 45229-3039
      • Investigational Site Number 840003
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • Investigational Site Number 840009
  • Virginia
    • Fairfax, Virginia, United States, 22030
      • Investigational Site Number 840002

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 25 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• The patient and/or their parent/legal guardian is willing and able to provide signed informed consent. If the patient is below the age of consent per local guidelines, he is willing to provide assent, if deemed able to do so.
• The patient must have a confirmed diagnosis of Fabry disease as documented by leukocyte α-galactosidase A (αGAL) of <4 nmol/hr/mg leukocyte (preferred assay; results from a central laboratory). If the leukocyte αGAL activity assay is difficult to obtain, the patient may be enrolled based on documented plasma αGAL <1.5 nmol/hr/mL (results from a central laboratory), with the agreement of the Genzyme Medical Monitor.

Exclusion Criteria:

• Patient has received prior treatment with enzyme replacement therapy (ERT) or oral pharmacological chaperone therapy for Fabry disease.
• Patient has received an investigational drug within 30 days of the screening visit.

• Patient is receiving any of the following medications and is clinically unable or unwilling to temporarily discontinue treatment with these medications for the indicated washout period prior to the renal function assessments until completion of these assessments:

  • Angiotensin converting enzyme inhibitors or angiotensin receptor blockers (6 week washout);
  • Non-steroidal anti-inflammatory drugs (3 day washout).
  • NOTE: Patients who are on chronic dialysis or have had a kidney transplant will not be required to discontinue the above medications because renal function assessments will not be performed in these patients.
• Patient has any contraindication mentioned in the labeling of iohexol. NOTE: patients with an eGFR <30 mL/min/1.73m^2 and patients who are on chronic dialysis or have had a kidney transplant may be enrolled irrespective of any contraindication to iohexol because iGFR will not be measured in these patients.
• Patient has any medical condition or extenuating circumstance which, in the opinion of the Investigator, could interfere with the patient's ability to complete all study procedures, or with the interpretation of study results (e.g., diabetes mellitus).
• The patient and/or their parent or legal guardian, in the opinion of the Investigator, is unable to adhere to the requirements of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Glomerular Filtration Rate by Plasma Iohexol Clearance (iGFR); Evaluations of renal and cardiac function	Drug: Iohexol; Evaluations of renal and cardiac function are standard-of-care in young patients with Fabry disease. This study uses the more precise iGFR measurement of renal function. No investigational drug will be administered in this study for the treatment of Fabry disease.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glomerular Filtration Rate Estimated from Serum Creatinine (eGFR)	Tests are performed only for patients who are not on chronic dialysis and/or have not received a kidney transplant.	Day 1 to Week 8
Glomerular Filtration Rate by Plasma Iohexol Clearance (iGFR)	Assessment of iGFR will NOT be performed if a patient is on chronic dialysis, has had a kidney transplant, or has a screening eGFR <30 mL/min/1.73 m^2 or presents any contraindication mentioned in the labeling of iohexol (Omnipaque™ 300).	Day 1 to Week 8
Protein Excretion Assessed from Three First-Morning Urine Voids		Day 1 to Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiovascular Function	Assessed by electrocardiogram (ECG) and echocardiography	Day 1 to Week 8

Collaborators and Investigators

• Sponsor: Genzyme, a Sanofi Company

Study record dates

Study Major Dates

• Study Start: May 1, 2013
• Primary Completion (Actual): September 1, 2016
• Study Completion (Actual): September 1, 2016

Study Registration Dates

• First Submitted: April 11, 2013
• First Submitted That Met QC Criteria: April 22, 2013
• First Posted (Estimate): April 25, 2013

Study Record Updates

• Last Update Posted (Actual): December 16, 2020
• Last Update Submitted That Met QC Criteria: December 11, 2020
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: Fabry disease
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Lipid Metabolism Disorders; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Cerebral Small Vessel Diseases; Lipidoses; Lipid Metabolism, Inborn Errors; Fabry Disease
• Other Study ID Numbers: AGAL19110; 2012-001966-14 (EudraCT Number); MSC 12711 (Other Identifier: Sanofi)